Candidate: Adit Ginde, MD, MPH is an Assistant Professor of Emergency Medicine at University of Colorado Denver (UCD). He has prior MPH and research fellowship training, and his early research career has focused on observational studies in vitamin D and acute respiratory infection (ARI). He seeks to transition from his institutional KL2 Award to this Beeson Career Development Award to focus on the role of vitamin D in the age related decline in immune function and specifically, response to infection and vaccine in older adults. Mentors/Environment: The primary mentor, Robert Schwartz, MD, is the Division Head of Geriatric Medicine and Director of the UCD Center on Aging. The co-mentor for immunology, Myron Levin, MD, is Professor of Medicine and Pediatrics at UCD, whose research has focused on characterizing and improving response to influenza and herpes zoster vaccines. Both are well-funded NIH clinical investigator and have mentored numerous junior faculty to successful independent careers in aging and immunology research. Training: The proposed Beeson career development plan builds on prior experience from fellowship and early career development awards to focus on three primary topical areas that require additional training: 1) Translational and Interventional Study Design;2) Aging/Nursing Home Research;and 3) Clinical Immunology. Dr. Ginde proposes intensive topical mentorship, focused coursework/seminars, and mentored research. Research: Infections are common in older adults resulting in increased healthcare utilization and morbidity. Vaccines improve host defense against pathogens and reduce the incidence, severity, and duration of common infections. However, the immune response to infectious pathogens and effectiveness of vaccines decline with advancing age. The ability of vitamin D supplementation to improve response to pathogens and vaccines in older adults has not been previously investigated in a clinical trial. In the context of a clinical trial of monthly oral high-dose vitamin D3 supplementation vs. standard dose vitamin D3 supplementation in older (age >60 years) long-term care residents, we propose the following specific aims: 1) Measure the efficacy of high dose monthly oral high-dose vitamin D3 supplementation (equivalent to 3,000-4,000 IU/day) compared to standard dose vitamin D3 supplementation (400-1,000 IU/day) in prevention of ARIs in 200 older (age ?? 60 years) long-term care residents;2) Determine the difference in specific humoral immune response to the inactive seasonal influenza vaccine by vitamin D3 supplementation dose and pre-vaccination serum 25- hydroxyvitamin D levels;3) Determine the difference in specific cell-mediated immune response to the live, attenuated zoster vaccine by vitamin D3 supplementation dose and pre-vaccination 25-hydroxyvitamin D levels. Summary: This innovative research plan;strong mentorship from geriatrics, infectious disease, immunology, and vaccine experts;and proposed career development experience will help Dr. Ginde become a leading investigator of interventions to improve immunosenescence and reduce the burden of infection in older adults. PUBLIC HEALTH RELEVANCE: As life expectancy increases, the increased incidence and severity of infection associated with aging has become a critical public health issue. Infection impacts the function, independence, and survival of older adults, and is a major contributor to healthcare utilization and costs. Through the proposed study, we will learn about the role of clinical interventions, particularly vitamin D, to improve the immune response to infection and vaccines, and ultimately reduce the incidence and severity of infection in older adults.